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Age‐Related Telomere Uncapping Occurs Independent of Telomere Shortening in Mouse Endothelial Cells
Author(s) -
Machin Daniel,
Dobson Parker,
Ghaffari Siavash,
Walker Ashley,
Lesniewski Lisa,
Donato Anthony
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.642.1
Subject(s) - telomere , senescence , in situ hybridization , inflammation , medicine , biology , andrology , dna , gene , genetics , gene expression
Arterial telomere dysfunction, characterized by shortening and/or uncapping, occurs with advancing age and has been associated with cardiovascular disease states. We have recently demonstrated that arterial telomere uncapping, but not shortening, is associated with age‐related p53‐mediated senescence and inflammation. Currently, it is unknown if arterial endothelial cells (ECs) exhibit telomere dysfunction similar to whole arteries. In primary EC cultures grown from aortic explants of young (n=6; Total ECs=419; age=6 mo) and old mice (n=3; Total ECs=197; age=31 mo), we measured telomere dysfunction‐induced foci (TIFs) as a marker of telomere uncapping. We quantified TIFs by co‐localization of p53 binding protein‐1, a DNA damage response element, with telomeres using immunofluorescent in situ hybridization (IF‐FISH). The percentage of ECs with > 5 TIFS, the amount previously associated with the onset of senescence, was two fold higher in old versus young ECs (13±4%, vs. 6±2% p<0.05). In general, there was a higher frequency of shorter telomeres in old compared to young ECs, and consistent with our previous whole artery analysis, mean telomere length, determined by FISH, was shorter in old compared to young ECs (104±33 vs. 308±71 AU, p<0.05). Whether from old or young mice, the length of telomeres containing TIFs was similar to those without TIFs (all p>0.05). These results are the first to demonstrate that telomere dysfunction is present in ECs from old mice. Furthermore, in support of our previous whole artery data, although EC telomeres shorten with age, EC telomere uncapping (TIFs) is not influenced by the shortening of individual telomeres.